Systems and methods for treating superficial venous malformations like spider veins

ABSTRACT

Systems and methods treat superficial venous malformations, such as spider veins. The systems and methods distribute a light-reactive agent, e.g., verteporfin, at or near an inner wall of a vein. The systems and methods activate the light-reactive agent by applying non-thermal light energy at a wavelength that activates the light-reactive agent to cause localize injury to the inner wall of the vein.

RELATED APPLICATION

This is a continuation patent application of U.S. patent applicationSer. No. 11/446,800, filed 5 Jun. 2006 now U.S. Pat. No. 7,465,312,which claims the benefit of U.S. Provisional Patent Application Ser. No.60/796,656, filed 2 May 2006, and entitled “Systems and Methods forTreating Superficial Venous Malformations Like Spider Veins,” which isincorporated herein by reference.

BACKGROUND OF THE INVENTION

As the large group of so-called baby-boomers advances in age, there areincreasing demands for effective, non-invasive treatment of vasculardiseases or dysfunctions affecting the vascular system. There are alsoincreasing demands for non-invasive cosmetic surgery to repairconditions that have vascular origins.

For example, spider veins result from various dysfunctions in the veins.Veins carry oxygen-poor blood from the body back to the heart.

Spider veins can be caused by the backup of blood, when one-way flapvalves in veins become weak, causing blood to collect in veins. Spiderveins can also arise due to other causes, e.g., hormone changes,inherited factors, and exposure to the sun. Spider veins are often redor blue and close to the surface of the skin. They can look like treebranches or spider webs with their short jagged lines. Spider veins canbe found on the legs and face. They can cover either a very small orvery large area of skin.

Sclerotherapy is a common treatment for spider veins. Sclerotherapyinvolves the injection of a solution into the vein that causes the veinwalls to swell, stick together, and seal shut. This stops the flow ofblood and the vein turns into scar tissue. Microsclerotherapy usesspecial solutions and injection techniques that can increase the successrate for removal of smaller spider veins. Sclerotherapy involvestedious, hard to learn injection techniques. It can lead to side effectslike stinging or painful cramps where the injection was made, ortemporary red raised patches of skin, or skin sores, or bruises. Thetreated vein can also become inflamed or develop lumps of clotted blood.Applying heat and taking aspirin or antibiotics can relieveinflammation. Lumps of coagulated blood can be drained.

Laser surgery can be used to treat larger spider veins in the legs.Laser surgery sends very strong bursts of light onto the vein, whichmakes the vein slowly fade and disappear. Laser surgery is moreappealing to some patients because it does not use needles or incisions.Still, when the laser hits the skin, the patient can feel a heatsensation that can be quite painful. Laser surgery can cause redness orswelling of the skin, and can cause burns and scars. Depending on theseverity of the veins, two to five treatments (15 to 20 minutes each)are generally needed to remove spider veins in the legs. Moreover, forspider veins larger than 3 mm, laser therapy is not very practical.Furthermore, the capital cost for purchasing trans-dermal lasers can bequite high, making the treatment relatively costly.

There is need for devices, systems, methods, and protocols that provideminimally invasive, cost effective, and patient-friendly surgical and/orcosmetic surgical treatment of superficial venous malformations, such ase.g., in the treatment of spider veins. There is also a need fordevices, systems, methods, and protocols that provide minimallyinvasive, cost effective, and patient-friendly treatment of diseases ordysfunctions in any region of the body that can be readily accessed bytreatment agents carried by blood; e.g., cancers like breast andprostrate cancer; ear, nose, and throat conditions; periodontal disease;and diseases of the eye.

SUMMARY OF THE INVENTION

The invention provides devices, systems, methods, and protocols thatprovide minimally invasive, cost effective, and patient-friendlysurgical and/or cosmetic surgical treatment of superficial venousmalformations, e.g., spider veins.

The invention also provides devices, systems, methods, and protocolsthat provide minimally invasive, cost effective, and patient-friendlysurgical treatment of diseases or dysfunctions in regions of the bodythat can be readily accessed by treatment agents carried by blood; e.g.,cancers like breast and prostrate cancer; ear, nose, and throatconditions; periodontal disease; and diseases of the eye.

According to one aspect of the invention, the devices, systems, andmethods distribute a light-reactive agent at, in, or near an inner wallof a vein. The devices, systems, and methods activate the light-reactiveagent by applying light energy at a wavelength that activates thelight-reactive agent to cause localize injury to the inner wall of thevein. The light energy is desirably non-thermal and is generated by alow voltage photoactivation device, comprising, e.g., one or morelight-emitting diodes. In one embodiment, the light-reactive agentcomprises verteporfin that is administered intravenously. Devices,systems, and methods that incorporate this aspect of the invention cantreat superficial venous disease, like spider veins.

The devices, systems, and methods improve the quality of patient care.The devices, systems, and methods eliminate side effects such asbrusing, burning, and skin discoloration. The devices, systems, andmethods do not require tedious, hard to learn injection techniques. Theydo not require high cost trans-dermal lasers. The devices, systems, andmethod are usable by a large group of practitioners, such asdermatologists, phlebologists, vascular surgeons, and interventionalradiologists.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a system of devices for treating asuperficial venous disease, such as spider veins using a light-reactiveagent, the agent being suited for intravenous injection.

FIG. 2 is a perspective view of the system shown in FIG. 1 packaged as akit, with directions for using the devices to treat a superficial venousdisease.

FIGS. 3A and 3B are side section views, taken generally alone line 3-3in FIG. 1, showing alternative embodiments of the internal components ofa photoactivation device that forms a part of the system shown in FIG.1.

FIGS. 4 to 14 show a representative method of using a system like thatshown in FIG. 1 to treat spider veins.

FIG. 15 shows an alternative embodiment of a source of a light-reactiveagent usable with the system shown in FIG. 1, the agent being in tabletor capsule form, for oral ingestion.

FIG. 16 shows an alternative embodiment of a source of a light-reactiveagent usable with the system shown in FIG. 1, the agent being in creamform for topical application.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Although the disclosure hereof is detailed and exact to enable thoseskilled in the art to practice the invention, the physical embodimentsherein disclosed merely exemplify the invention which may be embodied inother specific structures. While the preferred embodiment has beendescribed, the details may be changed without departing from theinvention, which is defined by the claims.

FIG. 1 shows devices that together comprise a system 10 for treating avascular disease or a dysfunction affecting the vascular system usinglight-reactive agents. The devices and system 10, and their associatedmethods of use, are particularly well suited for treating superficialvenous diseases, such as spider veins. For this reason, the devices andsystem 10, and their associated methods of use will be described in thiscontext.

Still, it should be appreciated that the disclosed devices and system10, and their associated methods of use are applicable for use intreating other diseases or dysfunctions elsewhere in the body that arenot necessarily related to spider veins or their cause, but arenevertheless capable of treatment by light-reactive agents carried byblood. Other conditions that can be treated by light reactive agentsusing the system 10 or a form of the system 10 include cancer, e.g.,breast or prostrate cancer; conditions of the ear, nose, or throat;periodontal disease; and conditions of the eye or sight (opthalmology).

As FIG. 1 shows, the system 10 includes at least one source 12 of aselected light reactive agent 14. The source 12 can be provided invarious forms. For example, as shown in FIG. 1, the source 12 cancomprise a conventional vial 16 containing the light reactive agent 14in solution suited for intravenous injection. Alternatively, the source12 can comprise the light reactive agent 14 packaged with a carrier intablet or capsule form for oral ingestion; or incorporated into a creamthat can be applied topically to the skin.

The light reactive agent 14 can comprise any light-reactive drug suitedfor photodynamic therapy (PDT). PDT is a treatment that uses an agent ordrug, also called a photosensitizer or photosensitizing agent, and lightenergy of a particular selected wavelength. The photosensitizers, whichare inert by themselves, bind to proteins found in blood, e.g.,lipoproteins. The proteins act as carriers, transporting thephotosensitizers to cells targeted for treatment. When exposed to lightof the particular wavelength (which varies according to thephotosensitizer), the photosensitizer reacts with oxygen. The reactiontransforms the oxygen into singlet oxygen and free radicals. The singletoxygen and free radicals disrupt normal cellular functions and causecell death.

The light reactive agent 14 can be selected among a group ofphotosensitizers, depending upon type and location of tissue beingtreated, as well as the mode contemplated for its introduction into bodytissue. Each photosensitizer is activated by light of a specificwavelength. This wavelength determines how far the light can travel intothe body. Thus, the physician can select a specific photosensitizer andwavelength(s) of light to treat different areas of the body.

In use, whatever the form, the selected light reactive agent 14 isadministered by the system 10 for delivery to a targeted tissuetreatment site at, in, or near an inner wall of a vein. In the contextof the illustrated embodiment, the targeted tissue site is a sub-dermalregion where one or more spider veins are present (this is shown FIG. 4and will be described in greater detail later).

The form for administration will depend upon the form of the source 12.The light reactive agent 14 can be provided in tablet or capsule form 54(see FIG. 15), which can be ingested orally for absorption by the GItract for systemic distribution by blood to the targeted tissuetreatment site. The light reactive agent 14 can be incorporated into acream form 56 (see FIG. 16), and the light reactive agent 14 can beapplied topically for percutaneous absorption by the skin to thetargeted tissue treatment site.

It has been discovered that an injectable form of the porphyrin-basedphotosensitizer called verteporfin—commercially available from QLT, Inc.as VISUDYNE® material (verteporfin for injection)—can be intravenouslyadministered to effectively treat spider veins using the system 10 shownin FIG. 1. Therefore, FIG. 1 shows the light reactive agent 14 insolution in the vial 16.

VISUDYNE® material has been used, together with a special laser light,to treat abnormal blood vessel formation in the eye, called age-relatedmacular degeneration (AMD) (which, if untreated, can lead to loss ofeyesight). VISUDYNE® material can be activated by shining apre-calculated dose of light at a particular (wavelength 689 nm) by alow-energy laser or light source 12 into the affected area of tissue.

In the context of the illustrated embodiment, where the source 12comprises an injectable solution of the light reactive agent 14, thedevice takes the form of a conventional hand-held syringe 18. Thesyringe 18 draws the light reactive agent 14 in solution from the vial16 (as shown in FIG. 6) and injects the photodynamic material insolution into the vascular system for transport by the blood flow to thetargeted tissue site (as shown in FIG. 7). Instead of a handheld syringe18, the administration device can take the form of a conventionalintravenous (IV) delivery catheter or set coupled to a syringe or otherintravenous delivery device or pump.

As FIG. 1 also shows, the system 10 includes a photoactivation device20. The photoactivation device 20 includes one or more light sources 22(see FIG. 3). The light sources 22 have a wavelength or a range ofwavelengths. The photoactivation device 20 also includes means forcontrolling the intensity or a range of intensities, spot size or arange of spot sizes, and other operating characteristics of the lightsources 22 that are conducive to activation the light reactive agent 14in a desired manner. Desirably, the photoactivation device 20 comprisesnon-thermal light energy generated by a low-voltage source (not greaterthan 12 Volts).

The photoactivation device 20 can take various forms, depending uponnature, location, and size of the targeted tissue region. Thephotoactivation device 20 can, e.g., be mounted on an adjustable framethat is located above or below the targeted tissue region of anindividual. The photoactive device may, alternatively, deliver lightthrough fiber optic cables and the like to areas inside the body. Forexample, a fiber optic cable can be inserted through an endoscope into atargeted internal tissue region (e.g., within a vessel or hollow organ)to treat a dysfunction. Alternatively, the photoactivation device 20 maycomprise a portable light source that applies light to surface tissue.

In the context of the illustrated embodiment (see FIGS. 1 and 3A/3B),the photoactivation device 20 is sized and configured to be held andmanipulated in a single hand, so that it can be wanded or waved to applylight percutaneously to a tissue region where the spider vein or veinsare located.

In this embodiment (see FIGS. 3A and 3B), the photoactivation device 20includes a low-energy light source 22 carried within a housing 24. Thehousing 24 comprises a handle end 26 and a light transmitting end 28.The handle end 26 is sized and configured to be conveniently gripped bya practitioner.

The handle end 26 encloses a control circuit 30 coupled to aself-contained low voltage (i.e., no more than 12 volts), DC powersource 32, such as a battery. The battery 32 is desirably rechargeable,e.g., by a plug-in connector (not shown), or, alternatively, the battery32 can be configured to be removed and replaced through a lift-off cover(also not shown). The handle end 26 includes an on-off switch 34, whichactivates the control circuit 30.

The light source 22 comprises one or more light emitters 36, which arecarried within the housing 24 for transmitting light from the lighttransmitting end 28 of the housing 24. The light emitters 36 are coupledto the control circuit 30.

In use, light can be applied to the skin in a tissue region where thespider vein or veins are located by holding the light transmitting end28 of the housing 24 out of direct surface contact with the skin.Alternatively, light can be applied to the skin in a tissue region wherethe spider vein or veins are located by placing the light transmittingend 28 of the housing 24 in direct surface contact with the skin. Withdirect surface contact between the skin and the light transmitting end28, reflectance toward the operator is minimized. With direct surfacecontact between the skin and the light transmitting end 28, the skinacts as a light guide, allowing output flux to be maximized withoutlocalized heating.

The light emitters 36 can be, e.g., light emitting diodes (LED's),emitting light in the wave-length(s) that activates the light reactiveagent 14. The light emitting diodes of a single photoactivation device20 can be conditioned to deliver multiple wavelengths, so that thephotoactivation device 20 can provide a universal platform for differentlight reactive agents 14. In the illustrated embodiment, where the lightreactive agent 14 is verteporfin, at least one of the wavelengths is 689nm. In this arrangement, the control circuit 30 may comprise a printedcircuit board on which the LED's are mounted.

The light emitters 36 can be arranged in an array sized and configuredto focus at common point. Small micro lenses (not shown) may be used toimprove focus and adjust the focal distance. In the embodimentillustrated in FIG. 3A, the light emitters 36 are oriented to focus at areflecting device 38 carried within the light transmitting end 28. Thereflecting device 38 reflects the light from the light emitters 36 out aportal 40 on the light transmitting end 28. The reflecting device 38 maycomprise, e.g., a surface mirror or a prism. The common focal point forall the light emitters 36 may be slightly short of the reflecting device38 or slightly beyond the reflecting device 38, so that the light fromthe reflecting device mirror will spread to cover an area, or spot size,beyond the portal 40. The reflecting device 38 may be made adjustable tochange the spot size during use.

Desirably, for ease of handling, the portal 40 is oriented at an angleto the main axis of the housing 24, preferably at about 90°. If desired,the light transmitting end 28 could be mounted for pivoting through arange of angles relative to the main axis, and/or for rotation about themain axis, to permit virtually infinite alignment of the emitted lightpath with the targeted tissue treatment site.

Alternatively, as shown in FIG. 3B, the light-emitters 36 can comprisean array of light emitting diodes carried in the portal 40, for applyingdiffused light directly from the portal 40 without use of a reflectingdevice.

As FIG. 1 shows, a removable transparent cover 42 can be provided tocover light transmitting end 28 during use. The cover 42 can comprise,e.g., plastic film encircled with an elastic material. The materials isselected to be substantially transparent to the wavelength of the lightemitted. Following use for a given individual, the cover 42 can beremoved and discarded, and replaced with a new cover for the nextindividual.

As FIG. 2 shows, the various components of the system 10 as justdescribed can be consolidated for use in a functional kit 44. The kit 44can take various forms. In the illustrated embodiment, the kit 44comprises a sterile, wrapped assembly including an interior tray 46made, e.g., from die cut cardboard, plastic sheet, or thermo-formedplastic material, which hold the contents. The kit 44 also preferablyincludes directions 48 for using the contents of the kit 44 to carry outa desired procedure.

In the illustrated embodiment, every component of the system 10 iscontained within the kit 44. Of course, various components can beprovided in separate packaging. In this arrangement, the directions 48still instruct use of the various components separately provided as asystem 10.

The directions 48 can, of course vary. The directions may be physicallypresent in the kit 44, but can also be supplied separately. Thedirections 48 can be embodied in separate instruction manuals, or invideo or audio tapes, CD's, and DVD's. The instructions for use can alsobe available through an internet web page. The directions 48 instructthe practitioner how to use the system 10 to carry out the intendedtherapeutic treatment. The directions 48 incorporate a method oftreatment using the system 10.

FIGS. 4 to 14 show a representative method of using the system 10 shownin FIG. 1 to treat a vascular condition such as spider veins, which thedirections 48 can express in part or in its entirety. As FIG. 4 shows,the method identifies a site where the targeted condition exists, i.e.,where the spider veins are present. This site is called the targetedtreatment site 50. The spider veins are usually easily identifiable by atrained practitioner. They are often red or blue and close to thesurface of the skin. They possess branches or “spider webs” with shortjagged lines. Spider veins can be found on the legs and face. They cancover either a very small or very large area of skin.

In the illustrated embodiment, the light reactive agent 14 is to beadministered intravenously. In this arrangement, an appropriateinjection site 52 is identified, as shown in FIG. 5. The injection site52 is where a selected light reactive agent 14 will administeredintravenously by the system 10 for delivery to the targeted treatmentsite 50. Desirably, the injection site 52 offers venous access at adistance from the targeted treatment site 50 in an upstream blood flowdirection (i.e., the injection site 52 is farther from the heart thanthe treatment site 50). In this manner, the light reactive agent 14,when injected intravenously, is allowed to become systemic and will beconveyed by venous blood flow toward the heart to the targeted treatmentsite 50.

As FIG. 6 shows, the method prepares the light reactive agent 14 forintroduction. In the illustrated embodiment, prescribed volume of thelight reactive agent 14 is drawn into the syringe 18. The volume to beinjected in dependent upon the therapeutic dose that is prescribed,which is, in turn, dependent upon the concentration of the lightreactive agent 14 in solution, as well as the morphology of the targetedtreatment site 50.

Typically, VISUDYNE® material is commercially reconstituted in saline orglucose solution at desired concentration of about verteporfin 2 mg/mL.At this concentration, a typical dose for a spider vein region can be inthe order of 1 cc to 5 cc, but this dosage will of course depend uponthe physiology of the individual, including the size and depth of thetarget treatment site 50, the skin type of the individual, and the bodysize of the individual. The dosage can be determined by clinical studyby physical measurements and titration, or can be selected empiricallybased upon general anatomic considerations, or a combination of theseand other considerations.

As FIG. 7 shows, the method injects the light reactive agent 14intravenously at the injection site 52. In the illustrated embodiment,the syringe 18 needle injects directly into a vein. An IV catheter maybe used, through which the light reactive agent 14 is injected bysyringe or other suitable IV pumping device.

The rate of delivery is dependent upon the nature and dosage of thelight reactive agent 14 as well as the physiology of the individualbeing treated. It is desirable to avoid discomfort to the individual,and the rate of delivery selected has this as its primary objective.

It is believed that, given the concentration and volume of the VISUDYNE®material being injected in the illustrated embodiment, an injectionperiod of 20 to 30 seconds is acceptable.

A period of time desirably occurs after injection (as the clocks C inFIGS. 7 and 8 indicate), to allow the light reactive agent 14 to becomesystemic. As FIG. 9 shows, verteporfin V, once injected, attaches tolipoproteins LP in the plasma. The lipoproteins LP carry the verteporinV to the targeted treatment site 50, as FIG. 10 shows. This exposesendothelium of the spider veins to the verteporin V carried by thelipoproteins LP.

The optimal time period to allow systemic distribution of the lightreactive agent 14 in this manner to the targeted treatment site 50following injection can be determined by clinical study by physicalmeasurements, or can be selected empirically based upon general anatomicconsiderations, or a combination of these and other considerations.

As FIG. 11 shows, after allowing a selected time period after injectionto pass, the method operates the photoactivation device 20 to applylight having prescribed characteristics to the targeted treatment site50. These prescribed characteristics include the wavelength and may alsoinclude, but are not necessarily limited to, a desired intensity, adesired spot size, and a desired duration of exposure. The wavelengthwill depend upon the light reactive agent 14 selected. The intensity,spot size, and duration of exposure of the applied light will dependupon the physiology of the individual being treated and the operatingparameters of the system 10, e.g., upon the size of the treatment site50; the depth of the treatment site 50; the skin type of the individual;the body size of the individual; the distance between the lighttransmitting end 28 of the housing 24 and the skin surface; the time ofexposure; and the pattern of applying the light. Optimal operatingcharacteristics for the photoactivation device 20 can be determined byclinical study by physical measurements, or can be selected empiricallybased upon general anatomic considerations, or a combination of theseand other considerations. The photoactivation device 20 can apply lighteither without making direct contact with the skin or by making directcontact with the skin.

As FIG. 12 shows, once verteporfin is activated by light in the presenceof oxygen, highly reactive, short-lived singlet oxygen and reactiveoxygen radicals are generated. The singlet oxygen and reactive oxygenradicals cause local damage to inner wall or endothelium of the veins.Cells outside of contact with the activated verteporfin, however, areleft unaffected.

Treatment by the system 10 and method just described intentionallycauses injury to the inner vein walls. By controlling the clinicallyparameters above described (i.e., the dosage, delivery time and rate,operating conditions of the photoactivation device 20, etc.) the natureof the injury can be tightly controlled and localized.

The initial injury to the vein wall evokes a healing process (see FIG.13). During the healing process, the vein heals shut over time. Thehealing results in shrinkage of the spider vein, and eventually,complete obliteration of the spider veins in the targeted region, asFIG. 14 shows.

It should be appreciated that the devices, systems, methods, andprotocols that have been described can provide minimally invasive, costeffective, and patient-friendly treatment of diseases or dysfunctions inall regions of the body that can be readily accessed by treatment agentscarried by blood; e.g., cancers like breast and prostrate cancer; ear,nose, and throat conditions; periodontal disease; and diseases of theeye.

The foregoing is considered as illustrative only of the principles ofthe invention. Furthermore, since numerous modifications and changeswill readily occur to those skilled in the art, it is not desired tolimit the invention to the exact construction and operation shown anddescribed. While the preferred embodiment has been described, thedetails may be changed without departing from the invention, which isdefined by the claims.

We claim:
 1. A system for treating a spider vein comprising: aphotosensitizing agent in solution sensitive to light energy at aselected wavelength, such that the photosensitizing agent generatessinglet oxygen and free radicals; a photoactivation device that emitslight energy at the selected wavelength, the photoactivation deviceconfigured to apply the light energy to a targeted treatment site wherethe spider vein exists, the light energy activating the photosensitizingagent to generate singlet oxygen and reactive oxygen radicals thatdisrupt normal cell functions and cause endothelial tissue cell death inan inner wall of the spider vein and evoke a healing process withoutaffecting non-endothelial tissue cells, where the healing process shutsand shrinks the spider vein in the targeted treatment site; a syringefor injecting a prescribed volume of the photosensitizing agent insolution at an intravenous injection site, the intravenous injectionsite offering venous access to the targeted treatment site spaced at adistance from the targeted treatment; and a timing device for measuringa prescribed time period to allow the photosensitizing agent to becomesystemic and be carried by blood into contact with endothelial tissue onan inner wall of the spider vein; wherein the photoactivation device isconditioned to deliver multiple wavelengths for use withphotosensitizing agents of different activation characteristics.
 2. Asystem according to claim 1 wherein the photosensitizing agent comprisesverteporfin.
 3. A system according to claim 1 wherein thephotoactivation device comprises a hand-held light source.
 4. A systemaccording to claim 1 wherein the photoactivation device includes atleast one light emitting diode.
 5. A system according to claim 1 whereinthe photoactivation device comprises a fiber-optic and endoscope thatreceives the fiber-optic cable.
 6. A system according to claim 1 whereinthe photosensitizing agent comprises an agent that binds to proteins inblood.